Influence of formulation on jet nebulisation quality of alpha(1) protease inhibitor

As foam appears during solution constitution and nebulisation of alpha(1) p rotease inhibitor (alpha(1) PI), we selected in a previous work, antifoams likely to be associated with an alpha(1) PI solution to be nebulised: span 65 at a 0.025% concentration and cetyl alcohol at a 0.05% concentration ass ociated with tyloxapol at 0.025% concentration. The purpose of this study w as, on the one hand to study the influence of the formulation on nebulisati on quality by relating physicochemical properties and nebulisation capacity , and on the other hand, to define the alpha(1) PT that will be retained fo r a clinical study. The properties of the different alpha(1) PI formulation s are compared: surface tension, viscosity, time required to constitute the protein solution and pH. Nebulisation quality is evaluated under different operating conditions by measuring the droplet size, the quantity of alpha( 1) PI nebulised, nebulisation time and the quantity of alpha(1) PI likely t o reach the lungs which was subjected to statistical analysis. The statisti cal analysis of results indicates that the addition of the cetyl alcohol/ty loxapol mixture improves nebulisation effectiveness by significantly increa sing the quantity of drug nebulised and therefore the quantity of alpha(1) PI likely to reach the lungs. It is this formulation that will be retained for clinical trials. We check that the nebuliser and operating conditions i nfluence all the parameters, that is to say the respirable fraction, the qu antity nebulised and the nebulisation time. Although there is no interactio n between the nebuliser and the formulation, nebulisation quality is the co mbined result of the formulation, the nebuliser and the operating condition s. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.